Antibody-based immunotherapy in high-risk neuroblastoma

Johnson, Erik E.; Dean, Shannon M.; Sondel, Paul M.

doi:10.1017/s1462399407000518

Cited by 25 publications

(45 citation statements)

References 112 publications

(188 reference statements)

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“…A fusion protein comprising anti-GD 2 mAb and IL2 (as a fusion) demonstrated anti-tumor responses in neuroblastoma patients [210]. This fusion construct has been reported to enhance the delivery of IL2 to tumor microenvironments and result in activation of natural killer cells, through IL2 binding to the cognate receptor, as well as tumor cell killing via ADCC mechanism [211,212].…”

Section: Figurementioning

confidence: 99%

Developments and Challenges for mAb-Based Therapeutics

et al. 2013

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The continuous increase in the number of approved monoclonal antibody (mAb)-based therapy suggests that mAbs, and their derivatives, will continue to be the focus of the biotherapeutics industry for years to come. Although vast improvements in our capability to manufacture, characterize, and stabilize mAbs have been achieved, there are still challenges to be overcome. These include analytical and stabilization approaches associated with the development of high concentration mAb formulations. In addition, several mAb-based modalities are under development, including antibody drug conjugates (ADCs), fusion proteins, and bispecific antibodies (bsAbs), all designed to overcome the limitations encountered with mAb therapy. The current status of their development, with emphasis on manufacturing challenges as well as preliminary clinical results, will be reviewed

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Section: Figurementioning

confidence: 99%

Developments and Challenges for mAb-Based Therapeutics

et al. 2013

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“…Neuroblastoma tumor associated antigens (TAAs) targeted by MAbs include the gangliosides GD2, GD3, and GM3 and the glycoproteins CD56, L1-CAM, and GP95 [26,27]. 3F8, a murine antibody targeting GD2, was the first MAb used in therapeutic clinical trials for patients with neuroblastoma [28], and treatment with 3F8 has resulted in clinical responses, including sustained complete responses, in children with neuroblastoma, especially in those with low disease burden [29,30].…”

Section: The Role Of Immunotherapy For Neuroblastomamentioning

confidence: 99%

New aspects of neuroblastoma treatment: ASPHO 2011 symposium review

Zage

Louis

Cohn

2012

Pediatric Blood & Cancer

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Neuroblastoma is the most common extracranial solid tumor of childhood, and the outcomes for children with high‐risk and relapsed disease remain poor. However, new international strategies for risk stratification and for treatment based on novel tumor targets and including immunotherapy are being employed in attempts to improve the outcomes of children with neuroblastoma. A new international neuroblastoma risk classification system has been developed which is being incorporated into cooperative group clinical trials in North America, Japan, and Europe, resulting in standardized approaches for the initial evaluation and treatment stratification of neuroblastoma patients. Furthermore, novel treatment regimens are being developed based on improved understanding of neuroblastoma biology and on the recruitment of the immune system to specifically target neuroblastoma tumors. These approaches will lead to new therapeutic strategies that likely will improve the outcomes for children with neuroblastoma worldwide. Pediatr Blood Cancer 2012; 58: 1099–1105. © 2012 Wiley Periodicals, Inc.

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“…Recent research and clinical trials led to innovative new drugs and targeted therapies against NB (10)(11)(12). Targeted therapies also consider the use of redox-modulating drugs.…”

Section: Introductionmentioning

confidence: 99%

Purified cranberry proanthocyanidines (PAC-1A) cause pro-apoptotic signaling, ROS generation, cyclophosphamide retention and cytotoxicity in high-risk neuroblastoma cells

Vorsa

2011

Int J Oncol

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Abstract. Optimized purification of oligomeric proanthocyanidines (PAC) from cranberry generated PAC-1A which selectively affected the viability of various neuroblastoma (NB) cell lines representing a spectrum of high-risk NB features. PAC-1A caused a loss of mitochondrial transmembrane depolarization potential (∆Ψm) and increased generation of reactive oxygen species (ROS) which was directly correlated to the modulation of apoptotic marker proteins in SMS-KCNR cells. PAC-1A reduced the expression of pro-survival (Bcl-2, MCL-1, Bcl-xL) and increased levels of pro-apoptotic (Bax, Bad, Bid) Bcl family proteins, upregulated the activity of SAPK/JNK MAPK and downregulated expression or activity of PI3K/AKT/mTOR pathway components. PAC-1A increased the cellular uptake/ retention of cyclophosphamide (CP). PAC-1A and CP synergistically increased cytotoxicity and expression of pro-apoptotic markers, reduced cellular glutathione (GSH) and superoxide dismutase (SOD) levels. Additional features of PAC-1A as an anticancer drug as shown in SMS-KCNR NB cells include delay of cell cycle progression and induction of cell death via TNF-family death receptor activity, thus, targeting both the extrinsic and intrinsic pathway of apoptosis. PAC-1A partially blocked the cell cycle in G2/M phase which correlated with a decrease of the G0/G1 subpopulation, upregulation of cyclin D1 and downregulation of CDK6 and p27 expression. In summary, PAC-1A has demonstrated chemotherapeutic potential to treat a broad spectrum of NBs including highly malignant tumors that show resistance to standard chemotherapeutics and apoptotic stimuli.

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Antibody-based immunotherapy in high-risk neuroblastoma

Cited by 25 publications

References 112 publications

Developments and Challenges for mAb-Based Therapeutics

Developments and Challenges for mAb-Based Therapeutics

New aspects of neuroblastoma treatment: ASPHO 2011 symposium review

Purified cranberry proanthocyanidines (PAC-1A) cause pro-apoptotic signaling, ROS generation, cyclophosphamide retention and cytotoxicity in high-risk neuroblastoma cells

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